Clément Lejealle1, Valérie Paradis2, Onorina Bruno3, Emmanuelle de Raucourt4, Claire Francoz1, Olivier Soubrane5, Didier Lebrec6, Pierre Bedossa2, Dominique Valla6, Hervé Mal7, Valérie Vilgrain8, François Durand6, Pierre-Emmanuel Rautou9. 1. Service d'Hépatologie, DHU Unity, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM, UMR-1149, Centre de Recherche sur l'Inflammation, Paris-Clichy, France. 2. Service d'Anatomie Pathologique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM, UMR-1149, Centre de Recherche sur l'Inflammation, Paris-Clichy, France; Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France. 3. Service d'Imagerie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. 4. Service d'Hématologie-Biologique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. 5. Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France; Service de Chirurgie Hépato-biliaire et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. 6. Service d'Hépatologie, DHU Unity, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM, UMR-1149, Centre de Recherche sur l'Inflammation, Paris-Clichy, France; Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France. 7. Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France; Service de Pneumologie B et Transplantation Pulmonaire, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France. 8. Service d'Imagerie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM, UMR-1149, Centre de Recherche sur l'Inflammation, Paris-Clichy, France; Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France. 9. Service d'Hépatologie, DHU Unity, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France; INSERM, UMR-970, Paris Cardiovascular Research Center-PARCC, Paris, France. University, Boston, MA. Electronic address: pierre-emmanuel.rautou@inserm.fr.
Abstract
BACKGROUND: Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect, defined by an increased alveolar-arterial oxygen gradient, induced by pulmonary vascular dilatations in the context of liver disease. The pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS are unknown. This study aimed at describing imaging and pathology changes associated with HPS. METHODS: We performed a case-control study in candidates for transplant with suspicion of cirrhosis. Each patient with HPS (Pao2 ≤ 70 mm Hg) was matched to three control subjects for age, cause, and liver disease severity. Pretransplant thoracic and abdominal imaging and explanted livers were reviewed. RESULTS: CT scans and Doppler ultrasounds from 21 patients with HPS were compared with those from 63 control subjects. HPS was associated with a two- to threefold higher prevalence of obstructed intrahepatic portal branches, of slowed or hepatofugal portal blood flow, and of large abdominal portosystemic shunts. Hepatic artery diameter was also larger in patients with HPS. Explanted livers from 19 patients with HPS were compared with those from 57 control subjects. HPS was associated with a fourfold higher prevalence of portal venule thrombosis and a ninefold higher prevalence of extensive vascular proliferation within fibrous septa. Obstruction of centrilobular venules, sinusoidal dilatation, and liver parenchymal extinction were also more common in patients with HPS. CONCLUSIONS: HPS is associated with intrahepatic vascular changes and with features suggesting severe portal hypertension. These results raise the hypothesis that intrahepatic vascular changes precipitate the development of HPS, opening new therapeutic perspectives for HPS.
BACKGROUND:Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect, defined by an increased alveolar-arterial oxygen gradient, induced by pulmonary vascular dilatations in the context of liver disease. The pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS are unknown. This study aimed at describing imaging and pathology changes associated with HPS. METHODS: We performed a case-control study in candidates for transplant with suspicion of cirrhosis. Each patient with HPS (Pao2 ≤ 70 mm Hg) was matched to three control subjects for age, cause, and liver disease severity. Pretransplant thoracic and abdominal imaging and explanted livers were reviewed. RESULTS: CT scans and Doppler ultrasounds from 21 patients with HPS were compared with those from 63 control subjects. HPS was associated with a two- to threefold higher prevalence of obstructed intrahepatic portal branches, of slowed or hepatofugal portal blood flow, and of large abdominal portosystemic shunts. Hepatic artery diameter was also larger in patients with HPS. Explanted livers from 19 patients with HPS were compared with those from 57 control subjects. HPS was associated with a fourfold higher prevalence of portal venule thrombosis and a ninefold higher prevalence of extensive vascular proliferation within fibrous septa. Obstruction of centrilobular venules, sinusoidal dilatation, and liver parenchymal extinction were also more common in patients with HPS. CONCLUSIONS: HPS is associated with intrahepatic vascular changes and with features suggesting severe portal hypertension. These results raise the hypothesis that intrahepatic vascular changes precipitate the development of HPS, opening new therapeutic perspectives for HPS.